Context dependence is a fundamental property of sensory perception; our perception of the outside world is not passive, but highly dependent upon our internal state (i.e. attention, desire) and ongoing behavior. For instance, if we feel something moving across the surface of our fingertips, it essential to know whether it is the object or our hand that is moving, when interpreting the nature of the object we are touching. Anatomical studies have shown that the movement (motor) and sensory regions of neocortex are highly interconnected, yet we know little about how signals from motor cortex influence sensory processing. We intend to study this sensorimotor integration at the network and cellular levels in the mouse whisker system, which is one of the primary modalities by which mice navigate their surroundings and is analogous to the human tactile sensory system. By using state-of-the-art optogenetics technology we are able to control the activity of neurons in motor cortex and measure cellular and network activity in somatosensory cortex. We have gathered exciting preliminary data that stimulating motor cortex can effectively alter the ongoing network activity in sensory cortex, which may in turn enhance the reliability of sensory responses. In this proposal, in a first set of experiments we intend to establish a mechanistic understanding of how motor cortex inputs influence cellular excitability and sensory responses in somatosensory cortex. These stimulation studies will be conducted in anesthetized mice, where motor and sensory pathways may be stimulated in an otherwise stable and rhythmic network dynamic. A second set of experiments will be conducted in awake mice, in order to determine the importance of the motor cortex inputs in the local regulation of network activity. By stimulating o suppressing activity in motor cortex and recording network activity in multiple sensory regions, we intend to determine whether this input can bi-directionally regulate local changes in network activity in awake mice. This research may potentially contribute to our understanding of the context dependence of sensory processing, and therefore enable a better understanding of sensory perception and motor coordination, be used as a general model for cortico-cortical regulation of sensory processing, and enhance our understanding of cortical deficits following damage to motor cortex as in ALS and stroke. PUBLIC HEALTH RELEVANCE: The ability of attention, motivation and behavior to modify our perception of the external world is a well known phenomenon, and yet the neural pathways involved in this process are poorly understood. Here we propose to study how a part of the brain that controls movement directly influences how the brain processes sensory information. This research has implications for understanding important pathways potentially contributing to movement and perceptual disorders.